The crucial early events in chemical oncogenesis are presumed to result from the interactions of chemical carcinogens with critical macromolecule(s). However, most of the known early phenotypic changes associated with chemical carcinogenesis bear no apparent direct or causal relationship to the oncogenic process. We recently reported an early event in liver carcinogenesis that is thus far unique, in that it directly involves the early actions of three types of hepatocarcinogens. Chemical carcinogen was found to interact principally with a specific polypeptide of molecular size 14,700 daltons (2S) in liver early during carcinogenesis. Short term ingestion of carcinogen causes marked reductions in the amounts of both the carcinogen-polypeptide complex and the polypeptide itself. Three kinds of liver carcinogens act in this way: the aromatic amamide, N-2-fluorylacetamide (FAA); the aminoazo dye, 3'-methyl-4-dimethylaminoazobenzene; and the amino acid analog, ethionine. This laboratory also previously reported another early event that occurs during liver carcinogenesis by FAA. Continued ingestion of FAA causes a marked elevation in the quantity of a carcinogen-protein complex of approximately 150,000 daltons molecular size (7.5S). We recently found that early during liver carcinogenesis by all three above carcinogens, the lowering in amount of the 14,700 daltons (2S) complex appears to be coupled with the increase in quantity of the 7.5S complex. Further, these reciprocal changes in content of the two complexes correlate in time with early histopathological alterations in the livers brought about by the three carcinogens. The biological significance of these early changes will be explored.